Clinical Impact of the Increase in Immunosuppressive Cell-Related Gene Expression in Urine Sediment during Intravesical Bacillus Calmette-Guérin.
Bacillus Calmette-Guérin
intravesical recurrence
myeloid-derived suppressor cell
non-muscle invasive bladder cancer
regulatory T cell
tumor-associated macrophage
Journal
Diseases (Basel, Switzerland)
ISSN: 2079-9721
Titre abrégé: Diseases
Pays: Switzerland
ID NLM: 101636232
Informations de publication
Date de publication:
18 Jun 2019
18 Jun 2019
Historique:
received:
19
04
2019
revised:
08
06
2019
accepted:
17
06
2019
entrez:
21
6
2019
pubmed:
21
6
2019
medline:
21
6
2019
Statut:
epublish
Résumé
The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers. Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils. Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6-8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0-1 genes upregulated, while 10 (42%) had 2-4 genes with increased expression. No patient in the 0-1 group experienced recurrence, while 70% of patients in the 2-4 group experienced recurrence ( Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment.
Sections du résumé
BACKGROUND
BACKGROUND
The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers.
METHODS
METHODS
Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils.
RESULTS
RESULTS
Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6-8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0-1 genes upregulated, while 10 (42%) had 2-4 genes with increased expression. No patient in the 0-1 group experienced recurrence, while 70% of patients in the 2-4 group experienced recurrence (
CONCLUSIONS
CONCLUSIONS
Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment.
Identifiants
pubmed: 31216733
pii: diseases7020044
doi: 10.3390/diseases7020044
pmc: PMC6630414
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : JSPS KAKENHI
ID : 16K20159
Organisme : JSPS KAKENHI
ID : 26861290
Organisme : Nara Medical University Grant-in-Aid for Collaborative Research Projects
ID : Fiscal Years 2015-2016
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